Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis.

Pullan, R. D.; Thomas, G. A. O.; Rhodes, Michael; Newcombe, R. G.; Williams, Gillian; Allen, Adrian; Rhodes, Jonathan M.

doi:10.1136/gut.35.3.353

Cited by 383 publications

(300 citation statements)

References 33 publications

Supporting

Mentioning

284

Contrasting

Unclassified

Order By: Relevance

“…The importance of mucus alteration in the initiation or perpetuation of UC has been widely studied over decades. During the active stage of UC, the mucus layer is severely disrupted and discontinuous with a 60%−70% decrease in thickness [26] . This is linked to the depletion of goblet cells and downregulation of mucin production which could be influenced by immunological or bacterial factors during inflammation.…”

Section: Cathelicidin and Inflammationmentioning

confidence: 99%

Cathelicidins in inflammation and tissue repair: Potential therapeutic applications for gastrointestinal disorders

Wong

et al. 2010

Acta Pharmacol Sin

View full text Add to dashboard Cite

Cathelicidins, a family of host defense peptides, are highly expressed during infection, inflammation and wound healing. These peptides not only have broad-spectrum antimicrobial activities, but also modulate inflammation by altering cytokine response and chemoattraction of inflammatory cells in diseased tissues. In this connection, a mouse cathelicidin has been demonstrated to prevent inflammation in the colon through enhancing mucus production and reducing production of pro-inflammatory cytokines. In addition, cathelicidins promote wound healing through stimulation of re-epithelialization and angiogenesis at injured tissues. In an animal model of gastric ulceration, the rat cathelicidin promotes ulcer healing by inducing proliferation of gastric epithelial cells both in vitro and in vivo. In conclusion, cathelicidins represent an important group of effector molecules in the innate immune system that operates a complex integration of inflammation and tissue repair in the gastrointestinal mucosa and other organs.

show abstract

Section: Cathelicidin and Inflammationmentioning

confidence: 99%

Cathelicidins in inflammation and tissue repair: Potential therapeutic applications for gastrointestinal disorders

Wong

et al. 2010

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…Mucins are required for the maintenance of an adequate mucus layer that covers the intestinal epithelium and thereby forms a physical barrier that protects the intestinal epithelium against toxic agents. The mucin MUC2 is the predominant mucin in the colon and MUC2 synthesis is diminished in UC [19,20] and presumably also NEC. It has been shown in cell line studies, experimental animal models and fresh human intestinal tissue specimens, that butyrate alters MUC2 expression in a dose dependent manner [21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

218 The Regulation of the Intestinal Mucin MUC2 Expression By Short Chain Fatty Acids: Implications for Epithelial Protection

Paassen¹,

Vincent²,

Puiman³

et al. 2009

Gastroenterology

View full text Add to dashboard Cite

“…Aberrant expression of MUC genes (8) as well as modifications of their transcription (34,45) have also been observed in inflammatory bowel disease. In addition, the thickness of the mucus layer is reduced in ulcerative colitis (33). On the other hand, mice knockout for Muc2 gene spontaneously develop adenocarcinoma in both small and large intestine (48).…”

mentioning

confidence: 99%

Butyrate specifically modulatesMUCgene expression in intestinal epithelial goblet cells deprived of glucose

Gaudier

Jarry²,

Blottière³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

278

176

View full text Add to dashboard Cite

The mucus layer covering the gastrointestinal mucosa is considered the first line of defense against aggressions arising from the luminal content. It is mainly composed of high molecular weight glycoproteins called mucins. Butyrate, a shortchain fatty acid produced during carbohydrate fermentation, has been shown to increase mucin secretion. The aim of this study was to test 1) whether butyrate regulates the expression of various MUC genes, which are coding for protein backbones of mucins, and 2) whether this effect depends on butyrate status as the major energy source of colonocytes. Butyrate was provided at the apical side of human polarized colonic goblet cell line HT29-Cl.16E in glucose-rich or glucose-deprived medium. In glucose-rich medium, butyrate significantly increased MUC3 and MUC5B expression (1.6-fold basal level for both genes), tended to decrease MUC5AC expression, and had no effect on MUC2 expression. In glucose-deprived medium, i.e., when butyrate was the only energy source available, MUC3 and MUC5B increase persisted, whereas MUC5AC expression was significantly enhanced (3.7-fold basal level) and MUC2 expression was strikingly increased (23-fold basal level). Together, our findings show that butyrate is able to upregulate colonic mucins at the transcriptional level and even better when it is the major energy source of the cells. Thus the metabolism of butyrate in colonocytes is closely linked to some of its gene-regulating effects. The distinct effects of butyrate according to the different MUC genes could influence the composition and properties of the mucus gel and thus its protective function. mucin; short-chain fatty acids; energy source; human colonic cell line THE MUCUS LAYER, COVERING the gastrointestinal mucosa, is considered the first line of defense against mechanical, chemical, or microbiological aggressions arising from the luminal contents (14). Mucus is mostly composed of mucins, i.e., glycoproteins of high molecular weight, whose protein backbones are encoded by MUC genes. So far, at least 15 different MUC genes have been identified in humans (15,32). In the large intestinal mucosa, the main MUC genes are MUC2, and to a lesser extent MUC1, MUC3, and MUC4. MUC2 codes for the main secreted mucin in the colon, whereas MUC1, MUC3, and MUC4 mainly code for membrane-located mucins but also present splicing variants coding for secreted mucins (50). Apart from their gel-forming protective function, some membrane-linked mucins, such as MUC1 (22) and MUC4 (12), exhibit specific functions in adhesion and cell signaling.MUC gene expression is altered in many colonic diseases. MUC2 is overexpressed in mucinous colorectal carcinoma, whereas its expression is particularly low in nonmucinous carcinoma (17, 43). MUC5AC and MUC6 expressions are abnormally induced in colon adenoma (6, 9). Aberrant expression of MUC genes (8) as well as modifications of their transcription (34, 45) have also been observed in inflammatory bowel disease. In addition, the thickness of the mucus layer is reduced in ulce...

show abstract

Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis.

Cited by 383 publications

References 33 publications

Cathelicidins in inflammation and tissue repair: Potential therapeutic applications for gastrointestinal disorders

Cathelicidins in inflammation and tissue repair: Potential therapeutic applications for gastrointestinal disorders

218 The Regulation of the Intestinal Mucin MUC2 Expression By Short Chain Fatty Acids: Implications for Epithelial Protection

Butyrate specifically modulatesMUCgene expression in intestinal epithelial goblet cells deprived of glucose

Contact Info

Product

Resources

About